Topical compositions and methods for reducing oxidative stress

Abstract

A composition for the topical application on a mammalian skin comprises one or more Brassica plant extracts selected from the group consisting of: Brassica juncea extract, Brassica oleracea italica extract, Brassica oleracea capitata extract, Brassica oleracea botrytis extract, and Brassica oleracea acephala extract. The composition further comprises one or more selected from the group consisting of: Curcuma longa extract, curcuminoids, tetrahydrocurcuminoids, metabolites of curcuminoids or tetrahydrocurcuminoids, and derivatives of curcuminoids or tetrahydrocurcuminoids. The composition further comprises one or more selected from the group consisting of: Camellia oleifera extract, Camellia sinensis extract, green tea extract and white tea extract; Wasabia japonica extract; Bacopa monnieri extract; Silybum marianum extract; and one or both of Piper nigrum extract or tetrahydropiperine.

What is claimed is: 
     
       1. A method of treating the skin of a mammal consisting essentially of:
 applying a therapeutically effective amount of a composition to the skin of the mammal to stimulate the cutaneous intrinsic defense in the mammal consisting essentially of: 
 one or more  Brassica  plant extracts selected from the group consisting of:  Brassica juncea  extract,  Brassica oleracea italica  extract,  Brassica oleracea capitata  extract,  Brassica oleracea botrytis  extract, and  Brassica oleracea  acephala extract; 
 one or more selected from the group consisting of:  Curcuma longa  extract, curcuminoids, tetrahydrocurcuminoids, tetrahydrodiferuloylmethane, tetrahydrodemethoxydiferuloylmethane, and tetrahydrobisdemethoxydiferuloylmethane; 
 one or more selected from the group consisting of:  Camellia oleifera  extract,  Camellia sinensis  extract, green tea extract, and white tea extract; 
   Wasabia japonica  extract; 
   Bacopa monnieri  extract; 
   Silybum marianum  extract; and 
 one or both of  Piper nigrum  extract or tetrahydropiperine. 
 
     
     
       2. The method of  claim 1 , wherein at least one of: tetrahydrodiferuloylmethane, tetrahydrodemethoxydiferuloylmethane, and tetrahydrobisdemethoxydiferuloylmethane is used in the method. 
     
     
       3. The method of  claim 1 , wherein the  Bacopa monnieri  extract, the  Silybum marianum  extract, the tetrahydropiperine, and the tetrahydrocurcuminoids are present in an amount ratio of about 2:2:1:1, respectively. 
     
     
       4. The method of  claim 1 , wherein the cutaneous intrinsic defense is one or more selected from the group consisting of:
 (a) controlling transcription of the Nrf2 target genes and Nrf2-regulated pathways to restore or maintain a desired cellular redox balance in the mammalian subject; 
 (b) up-regulating the Nrf2 target genes; 
 (c) restoring or maintaining a desired endogenous Nrf2 cellular level in the mammalian subject; 
 (d) regulating Nrf2 activity by cytoplasmic phosphorylation of Nrf2 through phosphotidylinositol 3-kinase catalytic subunit alpha (PIK3CA) and by formation of a nuclear complex Nrf2-prothymosin, alpha (PTMA) that prevents permanent induction of Nrf2-regulated genes; 
 (e) increasing an amount and activity of catalase in the mammalian subject; 
 (f) maintaining the balance between epidermal cell apoptosis and epidermal cell hyperproliferation; 
 (g) inhibiting the production of thymine dimers after exposure to UV-A and UV-B radiation; 
 (h) repairing DNA double strand breaks and modulating cell cycle progression to permit DNA repair; and 
 (i) increasing a thickness of the skin, a relief of the epidermal rete ridges, and/or a density of the collagen network in a papillary dermis. 
 
     
     
       5. The method of  claim 4 , wherein the Nrf2 target genes are one or more selected from the group consisting of: catalase (CAT), activating transcription factor 3 (ATF3), and peroxiredoxin 3 (PRDX3) genes. 
     
     
       6. The method of  claim 4 , wherein the (h) repairing DNA double strand breaks and modulating of cell cycle progression to permit DNA repair is triggered by the up-regulation of one or more of the genes selected from the group consisting of: BCLAF1, BRCC3, GHR, IMMT, SENP7, SMC1A, PTPN11, SMARCE1, SRRT, SUMO1, and TNFSF10. 
     
     
       7. A method of treating the skin of a mammal consisting essentially of:
 applying a therapeutically effective amount of a composition to the skin of the mammal to stimulate the cutaneous intrinsic defense in the mammal consisting essentially of: 
   Bacopa monnieri  extract; 
   Silybum marianum  extract; 
 a component selected from the group consisting of a  Curcuma longa  extract, curcuminoids, tetrahydrocurcuminoids, tetrahydrodiferuloylmethane, tetrahydrodemethoxydiferuloylmethane, and tetrahydrobisdemethoxydiferuloylmethane; 
 and 
 one or both of  Piper nigrum  extract or tetrahydropiperine; 
 
       wherein the components are in an amount ratio of about 2:2:1:1, respectively. 
     
     
       8. The method of  claim 7 , the composition consisting essentially of  Bacopa monnieri, Silybum marianum , tetrahydropiperine, and  Curcuma longa  extract. 
     
     
       9. The method of  claim 7 , wherein the cutaneous intrinsic defense is any one or a combination selected from the group consisting of:
 (a) controlling transcription of the Nrf2 target genes and Nrf2-regulated pathways to restore or maintain a desired cellular redox balance in the mammalian subject; 
 (b) up-regulating the Nrf2 target genes; 
 (c) restoring or maintaining a desired endogenous Nrf2 cellular level in the mammalian subject; 
 (d) regulating Nrf2 activity by cytoplasmic phosphorylation of Nrf2 through phosphotidylinositol 3-kinase catalytic subunit alpha (PIK3CA) and by formation of a nuclear complex Nrf2-prothymosin, alpha (PTMA) that prevents permanent induction of Nrf2-regulated genes; 
 (e) increasing an amount and activity of catalase in the mammalian subject; 
 (f) maintaining the balance between epidermal cell apoptosis and epidermal cell hyperproliferation; 
 (g) inhibiting the production of thymine dimers after exposure to UV-A and UV-B radiation; 
 (h) repairing DNA double strand breaks and modulating cell cycle progression to permit DNA repair; and 
 (i) increasing a thickness of the skin, a relief of the epidermal rete ridges, and/or a density of the collagen network in a papillary dermis. 
 
     
     
       10. The method of  claim 9 , wherein the Nrf2 target genes are one or more selected from the group consisting of: catalase (CAT), activating transcription factor 3 (ATF3), and peroxiredoxin 3 (PRDX3) genes. 
     
     
       11. The method of  claim 9 , wherein the (h) repairing DNA double strand breaks and modulating of cell cycle progression to permit DNA repair is triggered by the up-regulation of any one or more of the following genes: BCLAF1, BRCC3, GHR, IMMT, SENP7, SMC1A, PTPN11, SMARCE1, SRRT, SUMO1, and TNFSF10.